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Publication : Neural basis of opioid-induced respiratory depression and its rescue.

First Author  Liu S Year  2021
Journal  Proc Natl Acad Sci U S A Volume  118
Issue  23 PubMed ID  34074761
Mgi Jnum  J:314358 Mgi Id  MGI:6715811
Doi  10.1073/pnas.2022134118 Citation  Liu S, et al. (2021) Neural basis of opioid-induced respiratory depression and its rescue. Proc Natl Acad Sci U S A 118(23):e2022134118
abstractText  Opioid-induced respiratory depression (OIRD) causes death following an opioid overdose, yet the neurobiological mechanisms of this process are not well understood. Here, we show that neurons within the lateral parabrachial nucleus that express the micro-opioid receptor (PBL (Oprm1) neurons) are involved in OIRD pathogenesis. PBL (Oprm1) neuronal activity is tightly correlated with respiratory rate, and this correlation is abolished following morphine injection. Chemogenetic inactivation of PBL (Oprm1) neurons mimics OIRD in mice, whereas their chemogenetic activation following morphine injection rescues respiratory rhythms to baseline levels. We identified several excitatory G protein-coupled receptors expressed by PBL (Oprm1) neurons and show that agonists for these receptors restore breathing rates in mice experiencing OIRD. Thus, PBL (Oprm1) neurons are critical for OIRD pathogenesis, providing a promising therapeutic target for treating OIRD in patients.
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